Arbutamine is a new beta-adrenergic agonist with potent chronotropic and inotropic properties developed to pharmacologically induce stress. A prospective trial was conducted in five centers with a total enrolment of 45 patients with angiographically documented coronary artery disease. The primary purpose of the trial was to compare the efficacy of arbutamine with symptom-limited exercise in provoking clinical (angina), electrocardiographic (> or = 0.1 mV ST depression) and echocardiographic (induced wall motion abnormality) evidence of transient stress-induced ischemia. The secondary purpose was to assess the safety of arbutamine in patients with coronary artery disease. Ischemia was induced at a lower heart rate, systolic blood pressure and pressure-rate product during arbutamine infusion than during exercise. Using angina and/or electrocardiographic evidence of ischemia, arbutamine was more sensitive than exercise in detecting myocardial ischemia (77 vs. 58%, P = 0.021). Using echocardiography, the sensitivity for inducing wall motion abnormalities was 88% with arbutamine and 79% with exercise (P = not significant). Echocardiography in combination with angina and/or electrocardiographic evidence increased the sensitivity to 94% using arbutamine and to 88% with exercise. For the patients with multivessel disease, the sensitivity was 97% and 91%, respectively. No serious adverse events, either cardiac or noncardiac, were associated with arbutamine, and no patient had prolonged ischemia. Although exercise is the preferred method of stress for patients who are able to exercise adequately, arbutamine is at least as sensitive as exercise for the diagnosis of myocardial ischemia, and appears to be a safe and effective alternative to exercise testing in patients unable to exercise adequately.